1. Field of the Invention
The present invention relates to a crystal of luliconazole and a pharmaceutical preparation containing the crystal.
2. Brief Description of the Related Art
Luliconazole is an antifungal agent which has the structure shown below and which has an excellent action on fungi. At present, luliconazole is widely used as a pharmaceutical or medicine for treatment of infections caused by tinea pedis and tinea corporis, and will be used for treatment of infections caused by tinea unguium. In relation to the pharmaceutical preparation (medicament preparation) of luliconazole, recognized problems to be solved are that luliconazole is converted to stereoisomers, such as the SE isomer and the Z isomer, and that the crystallization of luliconazole occurs immediately after the application (see, for example, WO2007/102241; WO2007/102242; WO2007/102243; WO2009/031642; WO2009/031643; WO2009/031644). These problems limit the effectiveness of luliconazole as an antifungal agent. In particular, as for the isomerization, the present inventors have confirmed that both of the SE isomer and the Z isomer are influenced by the components of the preparation, temperature, and light. A storage condition of 3 weeks at 60° C. is used to evaluate the stability of luliconazole, in which the effects of the above factors are evaluated. To control undesirable conversion to stereoisomers, it has been necessary to shorten the heating step as much as possible in the production of luliconazole.
However, luliconazole has low water solubility. In order to dissolve luliconazole along with other components of a pharmaceutical preparation, it is necessary to perform a heating step. There is a need to develop any means for improving the solubility of luliconazole and shorten the heating time in the heating step. The shortening or reduction of the heating step reduces the generation or formation of any isomer generated or formed in this step and additionally the long-term stability is secured by lowering the initial isomer amount. In other words, the shortening or reduction of the dissolving step results in great improvement in quality.

A method is known, in which luliconazole as an active ingredient is produced by performing recrystallization from ethyl acetate and n-hexane (see, for example, JP9-100279A). However, nothing is known at all about recrystallization with alcohol or any step in which alcohol is added to an active ingredient. Therefore, nothing is known at all about a luliconazole crystal containing short chain alcohol(s) and a composition for an active pharmaceutical ingredient containing luliconazole crystal containing short chain alcohol(s).